Taletrectinib free base

SKU: orb1691639

Description

Taletrectinib free base (AB-106) is a potent, selective, and orally active small molecule inhibitor targeting ROS1 and NTRK kinases. It demonstrates low nanomolar IC50 values against wild-type ROS1, NTRK1/2/3, and several crizotinib-resistant ROS1 mutants like G2032R. This inhibitor is utilized in preclinical oncology research for studying targeted therapies in both cellular and animal models of ROS1- or NTRK-driven cancers.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1505514-27-1
• MW: 405.47
• Purity: 99.98% (May vary between batches)
• Formula: C₂₃H₂₄FN₅O
• SMILES: N([C@H](C)C1=CC(F)=CC=C1)C2=NN3C(=CN=C3C=C2)C4=CC=C(OC[C@@H](C)N)C=C4
• Target: ROS Kinase
• Solubility: DMSO:55 mg/mL (135.65 mM)

Bioactivity

• In Vivo:
  Taletrectinib free base (DS-6051b) (25 - 200 mg/kg; oral; once daily for 18 days) demonstrates anti-tumor activity in Balb-c nu/nu mice bearing U-118 MG cells. Taletrectinib free base (6.25 - 200 mg/kg; oral; once daily for 8 days) inhibits NTRK-rearranged cancer in Balb-c nu/nu mice harboring KM12 cells. Taletrectinib free base (3 - 100 mg/kg; p.o.; once daily for 4 days) induces rapid tumor regression in wild-type (WT) and G2032R mutant Ba/F3-carrying mice without severe weight loss.
• In Vitro:
  Taletrectinib free base (1-1000 nM; 72 h) has an IC50 of ~3 -20 nM against Ba/F3-TPM3-NTRK1, Ba/F3-ETV6-NTRK1, -NTRK2, -NTRK3, or KM12 cells. Taletrectinib free base (0.001-1000 nM; 2 h) dose-dependently inhibits ROS1 autophosphorylation in U-118-MG cells in vitro. Taletrectinib free base potently inhibits ROS1 autophosphorylation in JFCR-165, JFCR-168 and MGH193-1B cells. Taletrectinib free base partially inhibits phosphorylated NTRK1 at 10 nM and completely inhibits it at 100 nM. Taletrectinib free base potently inhibits recombinant ROS1, NTRK1, and NTRK3 in an ATP-competitive manner at subnanomolar concentrations. Taletrectinib free base at 0.2 μM almost completely inhibits ACK, ALK, DDR1, and LTK among the 160 kinases but does not strongly inhibit the other 152 kinases in the presence of 1 mM ATP. Taletrectinib free base effectively inhibits crizotinib-resistant ROS1 secondary mutations, including the G2032R solvent front mutation.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ROS Kinase, ROS1, ROSKinase, Taletrectinib, Taletrectinib free base, AB-106freebase, DS-6051b, DS-6051b free base, IBI344, IBI-344, IBI-344 free base, IBI 344

Compound Identifiers

PubChem CID

72202474